1,2-Dichloroethane → HCID 131734994, compound

HRID 923511Notes

Reaction equation

HRID 923511 reaction equation
[Si:1]([O:8][CH2:9][C@@:10]([C:13]1[N:14]=[N:15][N:16]([CH:18]([F:20])[F:19])[N:17]=1)([NH2:12])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.ClCCCl.Cl.[F:33][C:34]1[CH:54]=[CH:53][CH:52]=[C:51]([F:55])[C:35]=1[CH2:36][O:37][C:38]1[C:39]2[N:40]([C:44]([C:48](Cl)=[O:49])=[C:45]([CH3:47])[N:46]=2)[CH:41]=[CH:42][CH:43]=1>CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O>[C:4]([Si:1]([CH3:2])([CH3:3])[O:8][CH2:9][C@:10]([NH:12][C:48]([C:44]1[N:40]2[CH:41]=[CH:42][CH:43]=[C:38]([O:37][CH2:36][C:35]3[C:34]([F:33])=[CH:54][CH:53]=[CH:52][C:51]=3[F:55])[C:39]2=[N:46][C:45]=1[CH3:47])=[O:49])([C:13]1[N:14]=[N:15][N:16]([CH:18]([F:20])[F:19])[N:17]=1)[CH3:11])([CH3:5])([CH3:6])[CH3:7]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 86717885HCID 86717885, compoundHCID 90192603HCID 90192603, compound

Product 1

HCID 131734994HCID 131734994, compoundYield 79.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, to a mixture of 5.55 g of (2R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(difluoromethyl)-2H-tetrazol-5-yl]propan-2-amine, 7.5 ml of triethylamine, 220 mg of 4-dimethylaminopyridine, and 110 ml of 1,2-dichloroethane was added 8.88 g of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carbonyl chloride hydrochloride, followed by stirring at 70° C. for 2 hours. The reaction mixture was left to be cooled to room temperature, and was added to the mixture of water and ethyl acetate. The insoluble materials were separated by filtration and washed with ethyl acetate, and the aqueous layer was extracted with ethyl acetate. The organic layer was combined, washed with water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 8.70 g of N-{(2R)-1-{[tert-butyl (dimethyl)silyl]oxy}-2-[2-(difluoromethyl)-2H-tetrazol-5-yl]propan-2-yl}-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

  1. waitThe reaction mixture was left
  2. temperatureto be cooled to room temperature
  3. customThe insoluble materials were separated by filtration
  4. washwashed with ethyl acetate
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washwashed with water
  7. dry with materiala saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-94cce0f6bfbb4482836810b75f4f82a5
Source dataset
uspto-grants-2016_03
Patent number
US09278968B2

Reaction notes

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